Chronic obstructive pulmonary disease (COPD) commonly caused by smoking is a leading cause of morbidity and mortality worldwide and is currently the 5th leading cause of death in the westernized world [Rabe et al., 2007]. The World Health Organization (WHO) predicts that by 2020 COPD will rise from being the twelfth to the 5th most prevalent disease worldwide, and to the 3rd most common cause of death [Rabe et al., 2007]. Unlike asthma, where the relative understanding of the underlying pathophysiological mechanisms and clinical management of the disease are quite advanced, the same cannot be said for COPD, due to the complexity of the disease and the fact that it has only recently become the focus of clinical and basic research.
COPD is characterized by the slowly progressive development of poorly reversible airflow limitation. The disease includes chronic bronchitis with fibrosis and obstruction of small airways, emphysema leading to the enlargement of airspaces and destruction of lung parenchyma, and loss of lung elasticity [Rennard et al., 2002].
Disease pathology is reflected by chronic inflammatory processes as the obstruction of airways due to inflammatory cell infiltration and fibrosis along with inflammatory exudates in the lumen correlate with the severity of airflow obstruction [Hogg et al., 2004]. Hence, a large amount of research effort has focused on mediators of inflammation, the cells which secrete them, and their targets in the airways [Barnes et al., 2004].
The diagnosis of COPD is built upon the symptoms of cough and sputum production and/or exercise induced dyspnea along with a decreasing level of lung function as tested by spirometry (Global Initiative for Chronic Obstructive Lung Disease, Global strategy for the diagnosis, management and prevention of Chronic Obstructive Lung Disease. www.goldcopd.corn).
Because most patients first seek treatment when lung damage is already extensive (stage II COPD), there is a need for earlier disease detection and for a disease management tool [Csanky et al., 2007]. Economic and practical arguments justify the search for simple diagnostic tests, applicable in bedside or outpatient center settings, to replace the costly imaging technology and impractical spirometric tests used in hospitals and larger clinical centers.
One step global profiling of analyte (mRNA, protein, metabolite) biomarkers may soon replace conventional blood and histological/biopsy diagnostics technologies. It is important to establish whether the numerous blood and other body fluid derived potential novel diagnostics will be sufficiently efficacious and precise to replace, for example, imaging and functional diagnostic tests.
Currently, imaging technologies and spirometry are indispensable for the diagnosis and management of COPD. Both the diagnosis and management of COPD rely on costly and labor intensive lung function tests. Thus, there is an imminent need to replace the current diagnostic approaches with simpler clinical assays.
Amongst the many different classes of inflammatory mediators which have been suggested to play a role in COPD, lipid mediators derived from phospholipase metabolites appear to play an important role. We chose a set of precursor and end-stage, biologically active lipid metabolites and tested these in the BAL fluid of COPD patients and controls by mass spectrometry based quantitative methods.
As a first approach we focused on the BAL fluid which we obtained via a relatively invasive (bronchoscopy) albeit frequently used in diagnostic procedure. Bronchoaveolar lavage allows examination of the disease process “in-situ” by allowing the sampling of metabolites deep in the tissue at the level of bronchioles and alveolar ducts. We demonstrate the presence of a set of lipid metabolites that were measurable in the BAL fluid and support our goals to establish a correlation between lung function test results and lipid biomarker levels.